The present invention relates to microwave-assisted chemistry, and in particular relates to the measurement and control of ongoing microwave-assisted chemical reactions.
As generally recognized in the chemical arts, many chemical reactions can be initiated or accelerated by increasing the temperature (i.e., heating) of the reactants. Accordingly, carrying out chemical reactions at elevated (i.e., above ambient) temperatures is a normal part of many chemical processes.
The benefit of using microwave energy for elevating the temperature of a chemical reaction is well known. For example, U.S. Pat. No. 6,753,517 to Jennings, incorporated entirely herein by reference, discloses a microwave-assisted chemical synthesis instrument using controlled microwave energy.
Additionally, recent developments have increased the use of microwave energy for initiating, accelerating, or maintaining chemical reactions apart from temperature elevation. In some cases, microwaves are usefully applied while keeping reaction temperatures moderate, or even cool (i.e., at or below room temperature).
Monitoring various parameters of microwave-assisted chemistry can be helpful in controlling the input of microwave energy. For example, U.S. Pat. No. 5,972,711 to Barclay et al., also incorporated entirely herein by reference, describes a method for microwave-assisted chemical processes that includes monitoring the temperature of a mixture of reagents to maintain the reagents at or closely about a predetermined temperature.
In another example, U.S. Pat. No. 6,227,041 to Collins et al., also incorporated entirely herein by reference, describes a method and apparatus for measuring volatile content of samples. The method includes monitoring the weight and temperature of the sample during the application of microwave energy. The method further includes moderating the application of microwave power based on the measured temperature to prevent burning the sample.
In yet another example, U.S. Pat. No. 6,288,379 to Greene et al., also incorporated entirely herein by reference, describes a method for the use of continuously variable power in microwave-assisted chemistry. The method includes measuring and moderating the duty cycle of applied microwave power based on a measured selected parameter of a sample at a predetermined set point. The preferred measured parameters include temperature and pressure.
The aforementioned instruments and methods are exemplary for their respective applications. In addition, all benefit from a feedback control mechanism. The feedback control mechanism is based on at least one measured parameter, which may include temperature, pressure, volatile content, or weight, by means of example. These parameters are measured using standard instruments, e.g., an infrared pyrometer for measuring temperature and a pressure transducer for measuring pressure.
Chemical processes are commonly evaluated with respect to contaminants and product yield, for example. In this regard, spectrometers are well known to evaluate and monitor chemical samples, processes, or both for these and other criteria. Defined in general terms, spectroscopy is the physics of the theory and interpretation of interactions between matter and electromagnetic radiation. Electromagnetic radiation may be considered a stream of energy called quanta or photons. The amount of energy in each quantum determines the wavelength of the radiation.
Electrons orbiting atoms typically occupy a “ground state,” or the lowest energy level. Bonding between atoms forms a molecule, resulting in a new electron ground state energy level. Under certain conditions, an electron may acquire energy which elevates it to a higher energy level (i.e., an “excited state”). Electrons in atoms, functional groups, or molecules may change their energy level only when distinct quanta of radiation are absorbed or emitted by the molecule. The frequency of the absorbed or emitted radiation is a direct function of the change in energy of the electron. Thus, spectroscopy is the measurement of absorption and emission spectra. Because the amounts of energy absorbed or emitted are characteristic of particular atoms, molecules, and functional groups, spectroscopy is widely used to identify and quantify chemical compositions.
Based on wavelength, technique, or both, many different kinds of spectroscopy are scientifically useful. These include, but are not limited to, infrared (IR) absorption spectroscopy, fluorescence spectroscopy, ultraviolet/visible (UV/VIS), and Raman spectroscopy.
U.S. Patent Publication No. 2003/0116027 to Brulls discloses a method of monitoring a freeze drying process utilizing spectroscopy. The Brulls patent publication discloses that real-time spectroscopic analysis of the freeze-drying process may be used for feedback control of the process based on extracted measurement values, such as temperature and moisture content.
Microwave-assisted chemical synthesis is commonly performed in sealed reaction vessels. This presents a problem with respect to measuring certain reaction parameters, e.g., contaminant formation via side reactions and product yield. Currently, microwave-assisted techniques must monitor these and other parameters using an invasive technique or at least some physical contact with the vessel or its contents (e.g., a pressure transducer). See U.S. Pat. No. 6,630,652 to Jennings, for example.
Spectroscopy is a useful method to non-invasively monitor a reaction in progress. The reaction vessel is typically made of a microwave-transparent material, such as glass or quartz. Some spectroscopy methods, however, such as UV/VIS and IR spectroscopy, are impeded by glass because glass forms an opaque barrier to these wavelengths. Therefore, where glass vessels are desired or necessary, UV and IR spectroscopy are less attractive and potentially useless. Raman spectroscopy is an attractive alternative to U/VIS and IR in this respect because glass is substantially transparent to many of the frequencies commonly used for Raman spectroscopy.
Briefly, Raman spectroscopy measures the vibrational energies of molecules differently than other spectroscopic methods. Raman spectroscopy is based on the measurement of inelastic, as opposed to elastic, scattering of photons by molecules. Scattering occurs following a collision between incident photon energy from an energy source, such as a laser, and a molecule. Elastic scattering of photons occurs when the incident photon energy equals the energy of the photons scattered in all directions after the collision. In this case, the scattered photons provide no information about the molecule.
In contrast, inelastic scattering occurs when incident photons gain or lose energy upon collision with a molecule. In this case, the scattered photons do provide information about the molecule. An in-depth review of the theory and practice of Raman spectroscopy is set forth in Handbook of Vibrational Spectroscopy (John Chalmers and Peter Griffiths, eds., 2001) and Handbook of Raman Spectroscopy: From the Research Laboratory to the Process Line (Ian R. Lewis and Howell G. M. Edwards, eds., 2001).
Raman spectroscopy has been utilized in microwave-assisted techniques to a limited extent. Stellman et al., used Raman spectroscopy to monitor microwave curing of an amine-cured epoxide as a function of time (Christopher M. Stellman et al., In Situ Spectroscopic Study of Microwave Polymerization, Applied Spectroscopy, (49)3, 1995). In this study, Raman spectra of the microwave-cured epoxy were continuously taken in situ over a 2.4 minute curing time. Spectra taken after this time frame (i.e., longer exposure) were discarded because the sample ignited from excess heat accumulation.
More recently, Pivonka and Empfield integrated a Raman probe with a commercial microwave synthesizer to provide real-time spectral feedback from organic reactions for real-time in situ analysis of yield, mechanisms, and kinetics in the microwave-assisted reactions (Don E. Pivonka and James R. Empfield, Real-Time in situ Raman Analysis of Microwave-assisted Organic Reactions, Applied Spectroscopy, (58)1, 2004).
The problem that persists in light of these references is the lack of a commercially viable instrument and method for non-invasive real-time feedback control of microwave-assisted chemical synthesis. Logically, another problem that follows is the lack of an instrument and method for self-optimizing microwave-assisted chemical synthesis based on real-time non-invasive spectral analysis.